title: Proteasome inhibition alleviates prolonged moderate compression-induced muscle pathology.
abstract: BACKGROUND
  The molecular mechanism initiating deep pressure ulcer remains to be elucidated. The present study tested the hypothesis that the ubiquitin proteasome system is involved in the signalling mechanism in pressure-induced deep tissue injury.
  
  
  METHODS
  Adult Sprague Dawley rats were subjected to an experimental compression model to induce deep tissue injury. The tibialis region of the right hind limb was subjected to 100 mmHg of static pressure for six hours on each of two consecutive days. The compression pressure was continuously monitored by a three-axial force transducer within the compression indentor. The left hind limb served as the intra-animal control. Muscle tissues underneath the compressed region were collected and used for analyses.
  
  
  RESULTS
  Our results demonstrated that the activity of 20S proteasome and the protein abundance of ubiquitin and MAFbx/atrogin-1 were elevated in conjunction with pathohistological changes in the compressed muscle, as compared to control muscle. The administration of the proteasome inhibitor MG132 was found to be effective in ameliorating the development of pathological histology in compressed muscle. Furthermore, 20S proteasome activity and protein content of ubiquitin and MAFbx/atrogin-1 showed no apparent increase in the MG132-treated muscle following compression.
  
  
  CONCLUSIONS
  Our data suggest that the ubiquitin proteasome system may play a role in the pathogenesis of pressure-induced deep tissue injury.
authors.affiliation: Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. htpsiu@inet.polyu.edu.hk
authors.forename: Parco M
authors.initials: PM
authors.lastname: Siu
authors.forename: Bee T
authors.initials: BT
authors.lastname: Teng
authors.forename: Xiao M
authors.initials: XM
authors.lastname: Pei
authors.forename: Eric W
authors.initials: EW
authors.lastname: Tam
mesh_terms: D000818:Animals; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology / Q000627:therapeutic use; D023421:Models, Animal; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D011312:Pressure / Q000009:adverse effects*; D003668:Pressure Ulcer / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D017695:Soft Tissue Injuries / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D018840:HSP70 Heat-Shock Proteins; C558795:Hspa1l protein, rat; D007976:Leupeptins; D009124:Muscle Proteins; D061988:Proteasome Inhibitors; D025801:Ubiquitin; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde